scholarly journals The Association of ADRA2A Genotype with Dexmedetomidine Dosage in Pediatric Patients 

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ashwin Biju ◽  
Katherine A. Gallaway ◽  
Todd C. Skaar ◽  
Emma M. Tillman

Background: Critically ill children in the pediatric intensive care unit (PICU) often require sedation with dexmedetomidine, an α2-adrenergic receptor (ADRA2A) agonist. In adults, evidence suggests an ADRA2A polymorphism (rs1800544) modulates the dexmedetomidine response. We hypothesize that pediatric patients with at least one wild-type allele (GG and GC) will require larger dexmedetomidine doses and a longer time to effective dose than patients with a variant genotype (CC). Methods: This study was approved by the institutional review board (IRB). Patients in the PICU, 1 week through 25 years of age, and sedated with dexmedetomidine for ≥ 2 days were approached for enrollment. Genomic DNA was extracted from blood or saliva before genotyping for rs1800544 with a custom designed TaqMan® Assay on the QuantStudio 12K Flex platform. Patient genotype was determined using TaqMan® Genotyper software. Patient data were collected from the electronic medical record. Results: Sixty-five patients were enrolled and genotyped. Twenty-six patients were homozygous variant (CC), 27 heterozygous (GC), and 12 wildtype (GG) for rs1800544. The maximum dose (mcg/kg/hr) was 0.75 ± 0.31, and 0.78 ± 0.32, in patients with and without a G allele, respectively (p=0.65). The mean doses were 0.59 ± 0.22 and 0.58 ± 0.24 in patients with and without a G allele, respectively (p=0.85). The time to effective dose (hrs) was 5.8 ± 12.0 for patients with a G allele and 4.0 ± 8.2 for patients with no G allele (p=0.74).  Conclusion:  Our hypothesis that the CC genotype would require lower doses of dexmedetomidine was not confirmed. Patients without a G allele required lower dexmedetomidine dosage and a longer time to achieve an effective dose, but these findings were not significant. This could be due to the small sample size or clinical factors that affect pediatric sedation.  An adequately powered study could determine the association of ADRA2A genotype with dexmedetomidine. 

1989 ◽  
Vol 38 (1-2) ◽  
pp. 65-69 ◽  
Author(s):  
Yoko Imaizumi

AbstractNation-wide data in Japan on births and prenatal deaths of 16 sets of quintuplets during 1974-1985 were analysed. Among the 16 sets, 3 sets were liveborn, 8 were stillborn, and 5 were mixed, with a stillbirth rate of 0.64 (51/80). Effects of sex, maternal age and birth order on the stillbirth rate were not considered because of the small sample size. Effects of gestational age and birthweight on stillbirth rate were also examined. The mean weight of the 40 quintuplet individuals was 1,048 g.


Parasitology ◽  
1984 ◽  
Vol 89 (2) ◽  
pp. 209-220 ◽  
Author(s):  
C. R. Kennedy

SummaryFollowing recent suggestions that a peaked host age–parasite abundance curve, concomitant with a decline in the degree of dispersion of parasites in the older age classes of hosts, can provide evidence of parasite-induced host mortality, the changes in mean abundance and over-dispersion of metacercarial stages of Diplostomum spathaceum, D. gasterostei, Tylodelphys clavata and T. podicipina in relation to fish age were studied in a field locality. The mean parasite burden of D. spathaceum, D. gasterostei and T. clavata increased with host age and the maximum mean burden was found in the oldest hosts. The variance to mean ratio also increased in D. gasterostei, but decreased in the oldest hosts in D. spathaceum and T. clavata. It is concluded that this decrease could be due to parasite-induced host mortality but could equally be due to death of parasites within the host or to changes in infection rate or could be a reflection of the small sample size of the oldest fish. The mean burden of T. podicipina declined gradually with host age, but the variance to mean ratio remained constant and it is concluded that this could be explained by death of the parasites within the host. None of these data or data from other localities provided clear and unambiguous evidence of host mortality induced by heavy infections of any of the four species, although they are consistent with such mortality and do not refute such a possibility. It is concluded that it may be just as difficult to detect and unequivocally demonstrate parasite-induced host mortality in metacercarial digenean–fish host systems as in any other parasite–host systems.


2017 ◽  
Vol 34 (9) ◽  
pp. 1947-1961 ◽  
Author(s):  
Marlos Goes ◽  
Elizabeth Babcock ◽  
Francis Bringas ◽  
Peter Ortner ◽  
Gustavo Goni

AbstractExpendable bathythermograph (XBT) data provide one of the longest available records of upper-ocean temperature. However, temperature and depth biases in XBT data adversely affect estimates of long-term trends of ocean heat content and, to a lesser extent, estimates of volume and heat transport in the ocean. Several corrections have been proposed to overcome historical biases in XBT data, which rely on constantly monitoring these biases. This paper provides an analysis of data collected during three recent hydrographic cruises that utilized different types of probes, and examines methods to reduce temperature and depth biases by improving the thermistor calibration and reducing the mass variability of the XBT probes.The results obtained show that the use of individual thermistor calibration in XBT probes is the most effective calibration to decrease the thermal bias, improving the mean thermal bias to less than 0.02°C and its tolerance from 0.1° to 0.03°C. The temperature variance of probes with screened thermistors is significantly reduced by approximately 60% in comparison to standard probes. On the other hand, probes with a tighter weight tolerance did not show statistically significant reductions in the spread of depth biases, possibly because of the small sample size or the sensitivity of the depth accuracy to other causes affecting the analysis.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 767-767
Author(s):  
Heinz-Josef Lenz ◽  
Eric Van Cutsem ◽  
Udit N. Verma ◽  
Marc Saltzman ◽  
Jyotsna Fuloria ◽  
...  

767 Background: The CORRECT trial (NCT01103323) showed that REG improves overall survival (OS) vs placebo (PBO) in patients with mCRC who failed approved therapies (OS HR 0.77; 1-sided p=0.0052; Grothey 2013). A total of 760 patients were randomized to REG (n=505) or PBO (n=255) in more than 100 centers across North America, Europe, Asia, and Australia. We conducted a post-hoc exploratory subgroup analysis of the 83 (11%) patients from 18 US centers. Methods: Eligible patients had an ECOG PS ≤1 and had received approved therapies, including a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab, and if KRAS wild-type cetuximab and/or panitumumab. Data from the overall cohort, including US patients, are provided for perspective. Descriptive statistics are shown. Results: Of the 83 US patients, 36 (43%) were randomized to PBO and 47 (57%) to REG. Baseline characteristics of the US group were consistent with the overall cohort: median age in the US was 58 yr (range, 34 – 85) vs 61 (22 – 85) overall, 49% of US patients were ECOG PS1 (vs 46%), and 46% received ≤ 3 treatments for mCRC (vs 52%). KRAS status mutant/wild-type was 57%/34% in the US vs 57%/39% overall. All patients in the trial had prior bevacizumab and 57% of US patients also had prior cetuximab and/or panitumumab (vs 51% overall). However, higher proportion of patients in the US were Black (11% vs 2%), KRAS status unknown (10% vs 4%), and had colon as the primary disease site (82% vs 65%). Mean percentages of planned REG dose were similar (76% US vs 79% overall) and mean REG treatment duration was 3.1 mos in US vs 2.8 mos overall. Rates of dose modifications REG/PBO were 87%/47% in the US vs 76%/38% overall and grade ≥3 adverse events REG/PBO were 74%/64% vs 78%/49%, respectively. Based on 44 total death events, the HR for OS in the US subgroup was 0.46 (95%CI 0.25 – 0.84) favoring REG; median OS was 4.7 mos for PBO, but could not be estimated for REG due to censored data. However, this analysis was based on a relatively small sample size and event count. Conclusions: Patients treated in the CORRECT study in the US appear similar to the overall cohort and results are generally consistent with the overall findings of the trial. Clinical trial information: NCT01103323.


2021 ◽  
Vol 42 (04) ◽  
pp. 333-338
Author(s):  
Priyanka Aggarwal ◽  
Ishan Kumar ◽  
Sunil Kumar Rao ◽  
K Pradhap ◽  
Vineeta Gupta

Abstract Introduction Pediatric cancer contributes <1% of all malignancies. Childhood cancer survival has improved dramatically with the use of more intensive chemotherapy regimens, better stratification, and improvement in supportive care with enhanced facilities in pediatric intensive care unit (PICU). Objective The aim of this study was to identify the risk factors responsible for poor outcome in critically ill children with malignancies admitted in PICU. Materials and Methods Sixty-four children with a primary diagnosis of malignancy admitted in PICU with disease or treatment related complications were enrolled retrospectively. The short-term outcome, that is, shifting from PICU to ward, was assessed in relation to the presence of febrile neutropenia, organ failure, hepatitis, acute renal failure as well as requirement of inotropes and mechanical ventilation. Death was considered as an adverse outcome in this study. Results The mean age of study population was 6.25 ± 3.91 and M:F ratio 2.4:1. The majority of children had hematological malignancies (81.25%), that is, pre-B acute lymphoblastic leukemia (ALL) (45.3%), non-Hodgkin lymphoma (21.3%), acute myeloid leukemia (12.5%), T ALL (10.9%), and Hodgkin lymphoma (3.1%). Few children also had retinoblastoma (4.7%) and Langerhans cell histiocytosis (1.6%). The mean duration of PICU stay was 3.16 ± 2.31 days. Sepsis (37.5%) was the most common indication for PICU admission, followed by metabolic disturbance (26.6%), respiratory failure (17.2%), neurological complaints (15.6%), and anaphylactic shock (3.1%). Children requiring mechanical ventilation (p < 0.001), inotrope support (p < 0.001), having acute renal failure (p = 0.001), and >1 organ failure (p < 0.001) were associated with adverse outcome. The overall survival at the time of discharge from PICU was 64%. Conclusion In the context of low- and middle-income countries, optimal resource utilization by early identification of risk factors for clinical deterioration is required to allow timely admission to PICU and delivery of life-saving therapy to salvageable patients.


Author(s):  
Azza A. M. H. Swar Aldahab ◽  
Abdalla O. Elkhawad ◽  
Ahmed S. A. Elsayed ◽  
Hanan B. Eltahir

Warfarin is a potent anticoagulant with a confirmed effectiveness when anticoagulation targets are attained, an issue, that is troublesome to reach due to the fact that warfarin has a narrow therapeutic index (NTI), that means they have a narrow window between their effective doses and those at which they produce adverse toxic effects. However, oral anticoagulation throughout genetics recommended a genotype guided dosing, but is it favourable over clinical based dosing? Objectives: To analyze the mean stable warfarin doses attained clinically within CYP2C9*2 and VKORC11639G&gt;A wild-type and variant genotype status in Sudanese patients. Method: Genotyping for the CYP2C9*2 and VKORC1-1639G&gt;A polymorphisms were accomplished with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) technique. The mean stable warfarin dose per genotype was defined as the mean stable warfarin dose related to the stable INR within target range within a genotype of each of CYP2C9*2 or VKORC11639G&gt; Agenes, using Analysis of Variance (ANOVA) as the statistical method. Results: Fifty-three stable patients with wild-type CYP2C9*1*1 genotype had a mean stable warfarin dose of 4.9 ± 2.1 mg, 5 patients who were heterozygous CYP2C9*1*2 genotype, had a mean stable warfarin dose of 5.0 ± 0.71mg, and 2 patients were homozygous mutant CYP2CP*2*2 genotype had a mean stable warfarin dose of 4.8 ± 0.3 mg. The results were statistically insignificant, P = 0.992.Sixteen unstable patients were of wild-type CYP2C9*1*1 genotype, 40 patients with heterozygous CYP2C9*1*2 genotype, and 4 with homozygous mutant CYP2CP*2*2 genotype, had mean stable doses of 5.32 ± 2.9, 6.5 ± 2.7 and 4.5 ± 0.71 mg respectively. The result was statistically insignificant, P = 0.508. Fifty-two stable patients were having wild-type VKORC1G/G genotype, 3 patients had heterozygous VKORC1G/A genotype and 3 patients had homozygous mutant VKORC1/AA genotype, these patients had mean stable doses of 5.41 ± 1.63, 4.8 ± 2.19 and 5.4 ± 0.99 mg respectively. The mean warfarin stable dose among homozygous mutant VKORC1A/A genotype was lower than among wild-type and heterozygous genotype profiles. This result was statistically not significant, P = 0.729.In the unstable group, 8 patients of wild-type VKORC1G/G genotype, had a mean stable warfarin dose of 7.34 ± 3.9 mg, 40 patients of heterozygous VKORC1G/A genotype had a mean stable warfarin dose of 5.21 ± 2.76 mg, and 10 patients of homozygous VKORC1A/A genotype had a mean stable warfarin dose of 4.3 ± 1.83 mg. The result was statistically insignificant, P = 0.067.Conclusion: In our study, as there were no significant differences between warfarin mean stable doses related to different CYP2C9*2 and VKORC11639G&gt;A genotypes, the evidence is not satisfactory to conclude that the conventional use of genotype guided warfarin dosing will correct stable warfarin dose among Sudanese patients.


The Auk ◽  
2003 ◽  
Vol 120 (2) ◽  
pp. 311-322
Author(s):  
Octavio R. Rojas-Soto

Abstract Geographic patterns of variation in morphological characters in the Curve-billed Thrasher (Toxostoma curvirostre) have been recognized by the description of seven subspecies. Twelve standard measurements, as well as three colorimetric characters and two color pattern characters, were analyzed to test whether subspecies limits predict patterns of variation. Measurement error was addressed by measuring each character three times and calculating the mean. A total of 821 male study skins were used, representing 29 locations. A variety of analysis revealed two major groups, an eastern and western group, divided by the Sierra Madre Occidental. Those two groups had previously been recognized as the curvirostre and palmeri groups, respectively. Those groups were also recovered by analysis of mtDNA. The two groups fulfill the requirements for species. The Tiburón Island (T. c. insularis) sample was distinct for several characters; however, small sample size precludes formal taxonomic recommendation. Within the two major groups, most characters showed incongruent clinal patterns of variation that did not match subspecies limits.


PEDIATRICS ◽  
1993 ◽  
Vol 92 (2) ◽  
pp. 248-251
Author(s):  
Joseph J. Stambouly ◽  
Ellen Kahn ◽  
Robert A. Boxer

Study objective. To examine the correlation between clinical diagnoses and autopsy findings in children who die in the pediatric intensive care unit (PICU). Design. Retrospective chart review. Setting. PICU of a university-affiliated hospital. Patients. A consecutive sample of patients who died in the PICU and had autopsies performed. Measurements and main results. Of 193 patients who died during the 7½year study period, 50 (6%) had autopsies performed. The mean age was 34.7 months (range 15 hours to 17 years), and the mean length of stay in the PICU was 12.2 days (range 2 hours to 60 days). Major admitting diagnoses included postoperative cardiac surgery (19), nonoperative cardiac disease (7), hematologic/malignant disorder (5), and acquired immunodeficiency syndrome (5). There were 5 cases (10%) where autopsy revealed a major finding that, if known prior to death, would have altered clinical management and might have resulted in cure or prolonged survival. In another 9 patients (18%) the autopsy revealed major findings that, if known prior to death, would not have altered management. Eight of these findings related to the cause of death and 2 of them involved the basic disease. There was no correlation between new findings and either patient age or length of stay in the PICU. Conclusions. Despite modern diagnostic techniques, the autopsy continues to reveal valuable and unsuspected information.


CJEM ◽  
2007 ◽  
Vol 9 (04) ◽  
pp. 250-259 ◽  
Author(s):  
Rose P. Mengual ◽  
Michael J. Feldman ◽  
Gord R. Jones

ABSTRACTIntroduction:Do not resuscitate (DNR) orders are commonly accepted in most health care settings, but are less widely recognized in the prehospital setting. We describe the implementation of and satisfaction with a prehospital DNR protocol that allows paramedics to honour verbal and non-standard written DNR requests.Methods:This prospective observational study reviewed all cardiac arrests in southeastern Ontario between March 1, 2003 and September 31, 2005. Following a verbal or non-standard written DNR request, paramedics completed a questionnaire and a follow-up structured telephone interview was conducted with surrogate decision makers (SDMs).Results:There were 1890 cardiac arrests during the study period, of which 86 met our inclusion criteria. Paramedic surveys were available for 82 cases (95%), and surrogate decision makers (SDMs) were successfully contacted in 50 (58%) of them. Two SDMs declined to be interviewed. The mean patient age was 72.7 (standard deviation 13.8) years and 65% were male. Sixty-three (73%) of DNR requests were verbal, and 23 (27%) were written. The mean paramedic comfort was rated 4.9 on a 5-point Likert scale (with 5 being “very comfortable” ) (95% confidence interval [CI] 4.9–5.0). The mean SDM comfort was rated by paramedics as 4.9 (95% CI 4.8 –4.9). SDMs reported comfort in withholding CPR in 47 of 48 cases (98%), and with paramedic care in all cases. One SDM stated that although it was consistent with the patient's wishes, she was uncomfortable having to make the DNR request.Conclusions:Satisfaction with this novel prehospital DNR protocol was uniformly high among paramedic and SDM respondents. It appears that such a protocol is feasible and acceptable for the prehospital setting. Our conclusions are limited by a small sample size, the lack of a comparison group, and limited follow-up.


2004 ◽  
Vol 12 (2) ◽  
pp. 154-158 ◽  
Author(s):  
Débora Dias da Silva ◽  
Camila da Silva Gonçalo ◽  
Maria da Luz Rosário de Sousa ◽  
Ronaldo Seichi Wada

Dental plaque removal is an important issue in health promotion. Toothbrushing is one of the main methods employed for such purpose, since it can prevent dental caries by means of the fluoride present in the dentifrice. Dentifrices might contain plaque disclosing agents and thus allow dental plaque observation. The aim of this study was to assess whether utilization of a plaque disclosing agent interfered with plaque removal among adolescents, as well as the difference between utilization of erythrosine tablets and dentifrices containing plaque disclosing agent. The sample was composed of 62 students from Piracicaba, SP, Brazil, aged 12 to 14 years old, divided into 3 groups: G1 or control group (toothbrushing without plaque disclosure); G2 (plaque disclosing with an erythrosine tablet and toothbrushing) and G3 (toothbrushing with dentifrice containing plaque disclosing agent). After toothbrushing, disclosure of the remaining dental plaque was performed in all groups with a fuchsin tablet and measured through the Simplified Oral Health Assessment Index (OHI-S), in two stages with a 2-month interval between them. The analysis of variance (ANOVA) showed that there was no difference in the OHI-S index between the groups (p>0.05), however the G3 displayed a higher proportion of students with plaque reduction (23%) than G2 (21%), besides the smallest difference in the mean remaining dental plaque. There was no difference between groups; however, it was suggested that the dentifrice with plaque disclosing agent had positive results in relation to the erythrosine tablet, even though the small sample size may have interfered with the results, indicating the need of complementary studies.


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